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Abstract The dynamics of soft microparticles enclosed in a droplet flowing in a channel is an unexplored fundamental problem that lies at the heart of numerous applications, including droplet-based microfluidics, tissue engineering and smart material synthesis. Here we show that enclosing a flexible capsule into a droplet can amplify the capsule’s deformation parameters in channel flow by up to two orders of magnitude. Previously unreported capsule equilibrium shapes in channel flow, including an oblate spheroid and a reversed bullet, have also been discovered. We propose two theoretical models to predict the equilibrium position of the capsule inside the droplet, and estimate the capsule deformation, respectively. The present study provides an effective but simple approach to enhance and control the deformation of soft particles in a flowing suspension, which may inspire widespread applications, from high-throughput single-cell mechanical phenotyping, enhanced cross-membrane drug delivery, to manufacturing shape-controlled non-spherical particles and artificial cells.

IntroductionThe automatic and precise classification of epilepsy types using electroencephalogram (EEG) data promises significant advancements in diagnosing patients with epilepsy. However, the intricate interplay among multiple electrode signals in EEG data poses challenges. Recently, Graph Convolutional Neural Networks (GCN) have shown strength in analyzing EEG data due to their capability to describe complex relationships among different EEG regions. Nevertheless, several challenges remain: (1) GCN typically rely on predefined or prior graph topologies, which may not accurately reflect the complex correlations between brain regions. (2) GCN struggle to capture the long-temporal dependencies inherent in EEG signals, limiting their ability to effectively extract temporal features.MethodsTo address these challenges, we propose an innovative epileptic seizure classification model based on an Iterative Gated Graph Convolutional Network (IGGCN). For the epileptic seizure classification task, the original EEG graph structure is iteratively optimized using a multi-head attention mechanism during training, rather than relying on a static, predefined prior graph. We introduce Gated Graph Neural Networks (GGNN) to enhance the model's capacity to capture long-term dependencies in EEG series between brain regions. Additionally, Focal Loss is employed to alleviate the imbalance caused by the scarcity of epileptic EEG data.ResultsOur model was evaluated on the Temple University Hospital EEG Seizure Corpus (TUSZ) for classifying four types of epileptic seizures. The results are outstanding, achieving an average F1 score of 91.5% and an average Recall of 91.8%, showing a substantial improvement over current state-of-the-art models.DiscussionAblation experiments verified the efficacy of iterative graph optimization and gated graph convolution. The optimized graph structure significantly differs from the predefined EEG topology. Gated graph convolutions demonstrate superior performance in capturing the long-term dependencies in EEG series. Additionally, Focal Loss outperforms other commonly used loss functions in the TUSZ classification task.

Abstract Introduction Improving the delivery of existing evidence‐based interventions to prevent and diagnose HIV is key to Ending the HIV Epidemic in the United States. Structural barriers in the access and delivery of related health services require municipal or state‐level policy changes; however, suboptimal implementation can be addressed directly through interventions designed to improve the reach, effectiveness, adoption or maintenance of available interventions. Our objective was to estimate the cost‐effectiveness and potential epidemiological impact of six real‐world implementation interventions designed to address these barriers and increase the scale of delivery of interventions for HIV testing and pre‐exposure prophylaxis (PrEP) in three US metropolitan areas. Methods We used a dynamic HIV transmission model calibrated to replicate HIV microepidemics in Atlanta, Los Angeles (LA) and Miami. We identified six implementation interventions designed to improve HIV testing uptake (“Academic detailing for HIV testing,” “CyBER/testing,” “All About Me”) and PrEP uptake/persistence (“Project SLIP,” “PrEPmate,” “PrEP patient navigation”). Our comparator scenario reflected a scale‐up of interventions with no additional efforts to mitigate implementation and structural barriers. We accounted for potential heterogeneity in population‐level effectiveness across jurisdictions. We sustained implementation interventions over a 10‐year period and evaluated HIV acquisitions averted, costs, quality‐adjusted life years and incremental cost‐effectiveness ratios over a 20‐year time horizon (2023–2042). Results Across jurisdictions, implementation interventions to improve the scale of HIV testing were most cost‐effective in Atlanta and LA (CyBER/testing cost‐saving and All About Me cost‐effective), while interventions for PrEP were most cost‐effective in Miami (two of three were cost‐saving). We estimated that the most impactful HIV testing intervention, CyBER/testing, was projected to avert 111 (95% credible interval: 110–111), 230 (228–233) and 101 (101–103) acquisitions over 20 years in Atlanta, LA and Miami, respectively. The most impactful implementation intervention to improve PrEP engagement, PrEPmate, averted an estimated 936 (929–943), 860 (853–867) and 2152 (2127–2178) acquisitions over 20 years, in Atlanta, LA and Miami, respectively. Conclusions Our results highlight the potential impact of interventions to enhance the implementation of existing evidence‐based interventions for the prevention and diagnosis of HIV.

To solve the engineering problem of the first tunnel lining cracking caused by the second tunnel construction of double-arch highway tunnels, a research method combining distributed optical-fibre monitoring, inversion analysis and numerical simulation that can reflect lining cracking was presented. Optical fibres were laid on opposite sides of the steel arches inside the first tunnel lining. Embedded optical-fibre monitoring was conducted continuously during the second tunnel driving. Based on the fibre-optic strain profile, the lining cracking was deduced and warned in time. The mechanical behaviour of the steel arch was investigated by the inversion analysis, which took into consideration the integrated impact of axial force and flexural moment. A two-dimensional (2D) load-structure method–based numerical model was established, considering the influence of different load distributions in each construction condition. The total strain rotating crack constitutive model was applied to reflect the cracking behaviour of concrete lining in the simulation, and the model was calibrated and verified in the laboratory. Comparative analysis between the simulated strain distribution and the distributed optical-fibre monitoring results was carried out. The deformation mode and crack distribution of the lining were analysed. The cracking mechanism was explained. Specifically, the second tunnel construction led to the loading at the top of the middle partition wall and the release of rock pressure in the first tunnel. Under these load changes, the secondary lining of the first tunnel cracked on the inner side of the top of the middle partition wall owing to tension, and compression-bending failure occurred near the right arch foot. Finally, the influence of the parameters on the lining force was analysed, and a construction optimisation scheme was proposed.

Background Paediatric neuroblastoma and brain tumours account for a third of all childhood cancer-related mortality. High-risk neuroblastoma is highly aggressive and survival is poor despite intensive multi-modal therapies with significant toxicity. Novel therapies are desperately needed. The Zika virus (ZIKV) can access the nervous system and there is growing interest in employing ZIKV as a potential therapy against paediatric nervous system tumours, including neuroblastoma. Methods Here, we perform extensive data mining, integration and re-analysis of ZIKV infection datasets to highlight molecular mechanisms that may govern the oncolytic response in neuroblastoma cells. We collate infection data of multiple neuroblastoma cell lines by different ZIKV strains from a body of published literature to inform the susceptibility of neuroblastoma to the ZIKV oncolytic response. Integrating published transcriptomics, interaction proteomics, dependency factor and compound datasets we propose the involvement of multiple host systems during ZIKV infection. Results Through data mining of published literature, we observed most paediatric neuroblastoma cell lines to be highly susceptible to ZIKV infection and propose the PRVABC59 ZIKV strain to be the most promising candidate for neuroblastoma oncolytic virotherapy. ZIKV induces TNF signalling, lipid metabolism, the Unfolded Protein Response (UPR), and downregulates cell cycle and DNA replication processes. ZIKV infection is dependent on sterol regulatory element binding protein (SREBP)-regulated lipid metabolism and three protein complexes; V-ATPase, ER Membrane Protein Complex (EMC) and mammalian translocon. We propose ZIKV non-structural protein 4B (NS4B) as a likely mediator of ZIKVs interaction with IRE1-mediated UPR, lipid metabolism and mammalian translocon. Conclusions Our work provides a significant understanding of ZIKV infection in neuroblastoma cells, which will facilitate the progression of ZIKV-based oncolytic virotherapy through pre-clinical research and clinical trials.

Early mutation identification guides patients with colorectal cancer (CRC) toward targeted therapies. In the present study, 414 patients with CRC were enrolled, and amplicon-based targeted next-generation sequencing (NGS) was then performed to detect genomic alterations within the 73 cancer-related genes in the OncoAim panel. The overall mutation rate was 91.5 % (379/414). Gene mutations were detected in 38/73 genes tested. The most frequently mutated genes were TP53 (60.9 %), KRAS (46.6 %), APC (30.4 %), PIK3CA (15.9 %), FBXW7 (8.2 %), SMAD4 (6.8 %), BRAF (6.5 %), and NRAS (3.9 %). Compared with the wild type, TP53 mutations were associated with low microsatellite instability/microsatellite stability (MSI-L/MSS) (P = 0.007), tumor location (P = 0.043), and histological grade (P = 0.0009); KRAS mutations were associated with female gender (P = 0.026), distant metastasis (P = 0.023), TNM stage (P = 0.013), and histological grade (P = 0.004); APC mutations were associated with patients

The economic operation of the integrated energy system faces the problems of coupling between energy production and conversion equipment in the system and the imbalance of various energy demands. Therefore, taking system safety as the constraint and minimum economic cost as the objective function, including fuel cost, operation, and maintenance cost, this paper proposes the operation dispatching model of the integrated energy system based on hydrogen fuel cell (HFC), including HFC, photovoltaic, wind turbine, electric boiler, electric chiller, absorption chiller, electric energy storage, and thermal energy storage equipment. On this basis, a distributionally robust optimization (DRO) model is introduced to deal with the uncertainty of wind power and photovoltaic output. In the distributionally robust optimization model, Kullback–Leibler (KL) divergence is used to construct an ambiguity set, which is mainly used to describe the prediction errors of renewable energy output. Finally, the DRO economic dispatching model of the HFC integrated energy system (HFC-IES) is established. Besides, based on the same load scenario, the economic benefits of hybrid energy storage equipment are discussed. The dispatching results show that, compared with the scenario of only electric energy storage and only thermal energy storage, the economic cost of the scenario of hybrid electric and thermal storage can be reduced by 3.92% and 7.55% respectively, and the use of energy supply equipment can be reduced, and the stability of the energy storage equipment can be improved.

Abstract The contra‐rotating machine (CRM) has been a preferable selection of the contra‐rotating propulsion system (CRPS) owing to its high efficiency, high compactness, and low noise. However, the conventional CRM with rotating stator has the problem of brush and slip ring, and the conventional brushless CRM has the problem of coordinated control of equal and opposite torque. Aiming at the above problems, this article proposes a transverse‐dislocated magnetic‐field modulated brushless contra‐rotating machine (TDMFM‐BCRM). The proposed TDMFM‐BCRM has some advantages of no rotating winding, no associated brushes and slip rings, and equal and opposite torques at any time, therefore it has good potential for the CRPS. The working principle of the TDMFM‐BCRM including three dimensional magnetic‐field modulated theory, back electromotive force (EMF) generation, and torque relation is studied. Then, the influences of main parameters including magnetic block parameters and PM sizes on torques are investigated. The critical electromagnetic performances of the TDMFM‐BCRM are analysed. A prototype of TDMFM‐BCRM is manufactured and measured to validate the above analysis. Finally, the comparison of the TDMFM‐BCRM and the existing schemes are analysed.

With the rapid development of the world economy, IGBT has been widely used in motor drive and electric energy conversion. In order to timely detect the fatigue damage of IGBT, it is necessary to monitor the junction temperature of IGBT. In order to realize the fast calculation of IGBT junction temperature, a finite element method of IGBT temperature field reduction is proposed in this paper. Firstly, the finite element calculation process of IGBT temperature field is introduced and the linear equations of finite element calculation of temperature field are derived. Temperature field data of different working conditions are obtained by finite element simulation to form the sample space. Then the covariance matrix of the sample space is constructed, whose proper orthogonal decomposition and modal extraction are carried out. Reasonable basis vector space is selected to complete the low dimensional expression of temperature vector inside and outside the sample space. Finally, the reduced-order model of temperature field finite element is obtained and solved. The results of the reduced order model are compared with those of the finite element method, and the performance of the reduced-order model is evaluated from two aspects of accuracy and rapidity.

Meningiomas, the most prevalent primary benign intracranial tumors, often exhibit complicated levels of adhesion to adjacent normal tissues, significantly influencing resection and causing postoperative complications. Surgery remains the primary therapeutic approach, and when combined with adjuvant radiotherapy, it effectively controls residual tumors and reduces tumor recurrence when complete removal may cause a neurologic deficit. Previous studies have indicated that slip interface imaging (SII) techniques based on MR elastography (MRE) have promise as a method for sensitively determining the presence of tumor-brain adhesion. In this study, we developed and tested an improved algorithm for assessing tumor-brain adhesion, based on recognition of patterns in MRE-derived normalized octahedral shear strain (NOSS) images. The primary goal was to quantify the tumor interfaces at higher risk for adhesion, offering a precise and objective method to assess meningioma adhesions in 52 meningioma patients. We also investigated the predictive value of MRE-assessed tumor adhesion in meningioma recurrence. Our findings highlight the effectiveness of the improved SII technique in distinguishing the adhesion degrees, particularly complete adhesion. Statistical analysis revealed significant differences in adhesion percentages between complete and partial adherent tumors (p = 0.005), and complete and non-adherent tumors (p

Abstract Understanding the molecular mechanisms that regulate grain yield is important for improving agricultural productivity. Protein ubiquitination controls various aspects of plant growth but lacks understanding on how E2-E3 enzyme pairs impact grain yield in major crops. Here, we identified a RING-type E3 ligase SGD1 and its E2 partner SiUBC32 responsible for grain yield control in Setaria italica. The conserved role of SGD1 was observed in wheat, maize, and rice. Furthermore, SGD1 ubiquitinates the brassinosteroid receptor BRI1, stabilizing it and promoting plant growth. Overexpression of an elite SGD1 haplotype improved grain yield by about 12.8% per plant, and promote complex biological processes such as protein processing in endoplasmic reticulum, stress responses, photosystem stabilization, and nitrogen metabolism. Our research not only identifies the SiUBC32-SGD1-BRI1 genetic module that contributes to grain yield improvement but also provides a strategy for exploring key genes controlling important traits in Poaceae crops using the Setaria model system.

Summary: Background: The US Ending the HIV Epidemic (EHE) initiative aims to reduce national HIV incidence 90% by 2030 and to address the disproportionate burden of HIV among different racial/ethnic populations. Florida's state-wide 2022–2026 Integrated HIV Prevention and Care Plan outlines objectives for reaching EHE goals. In Miami-Dade County, we determined the epidemiological impact of achieving the integrated plan's objectives individually and jointly. Methods: We adapted an HIV transmission model calibrated to Miami-Dade County adjusting access to HIV testing, pre-exposure prophylaxis (PrEP) and antiretroviral treatment to model the effects of each objective between 2022 and 2030. We compared two service scale-up approaches: (a) scale-up proportionally to existing racial/ethnic group access levels, and (b) scale-up according to new diagnoses across racial/ethnic groups (equity-oriented). We estimated reductions in new HIV infections by each objective and approach, compared to the EHE's incidence reduction target. Findings: The single most influential strategy was reducing new HIV diagnoses in Hispanic/Latinx men who have sex with men through increased PrEP uptake, resulting in 907/2444 (37.1%) fewer annual new HIV infections in 2030. Achieving all objectives jointly would result in 1537/2444 (62.9%) and 1553/2444 (63.5%) fewer annual new HIV infections with the proportional and equity-oriented approaches, respectively. Interpretation: Achieving the goals of Florida's integrated care plan would significantly reduce HIV incidence in Miami-Dade County; however, further efforts are required to achieve EHE targets. Structural changes in service delivery and a focus on effective implementation of available interventions to address racial/ethnic disparities will be crucial to ending the HIV epidemic. Funding: This work was supported by the National Institutes of Health/National Institute on Drug Abuse grant no. R01-DA041747.

Geographical differences are conspicuous in lung cancer, and the distinct molecular features of lung tumor between Western patients and Asian patients have been demonstrated. However, the etiology of non-small-cell lung cancer (NSCLC) and the distribution of associated molecular aberrations in China have not been fully elucidated. The mutational profiles of 12 lung cancer-related genes were investigated in 85 patients from eastern China and 88 patients from southern China who had been histologically confirmed NSCLC. Overall, 93.6% (162/173) of tumor samples harbored at least one somatic alteration. The most frequently mutated genes were TP53 (56.1%), EGFR (50.3%), and KRAS (14.5%). We found that EGFR mutated much more frequently (60.0% vs 40.9%, P = 0.012) and TP53 mutations had significantly lower incidence (47.1% vs 64.8%, P = 0.019) in eastern cohort than that in southern cohort. Mutational signature analysis revealed a region-related mutagenesis mechanism characterized by a high prevalence of C to T transitions mainly occurring at CpG dinucleotides in southern patients. This study reveals the difference in the mutational features between NSCLC patients in eastern and southern China. The distinct patterns of gene mutation could provide clues for the mechanism of carcinogenesis of lung cancer, offering opportunities to stratify patients into optimal treatment plans based on genomic profiles.

Abstract This study proposes to construct a model using random forest method, an efficient machine learning‐based method, to predict the spatial structure and temporal evolution of the sea surface temperature (SST) cooling induced by northwest Pacific tropical cyclones (TCs), a process of the so‐called wind pump. The predictors in use include 12 predictors related to TC characteristics and pre‐storm ocean conditions. The model is shown to skillfully predict the spatiotemporal evolutions of the cold wake generated by TCs of different intensity groups, and capture the cross‐case variance in the observed SST response. Another model is further built based on the same method to assess the relative importance of the 12 predictors in determining the magnitude of the maximum cooling. Computations of feature scores of those predictors show that TC intensity, translation speed and size, and pre‐storm mixed layer depth and SST dominate, depending on the area where the cooling is considered.

Abstract Metformin is the biguanide of hepatic insulin sensitizer for patients with non-alcohol fatty liver disease (NAFLD). Findings regarding its efficacy in restoring blood lipids and liver histology have been contradictory. In this study, we explore metformin’s preventive effects on NAFLD in leptin-insensitive individuals. We used liver tissue, serum exosomes and isolated hepatocytes from high-fat diet (HFD)-induced Zucker diabetic fatty (ZDF) rats and leptin receptor (Lepr) knockout rats to investigate the correlation between hepatic Lepr defective and liver damage caused by metformin. Through immunostaining, RT-PCR and glucose uptake monitoring, we showed that metformin treatment activates adenosine monophosphate (AMP)-activated protein kinase (AMPK) and its downstream cytochrome C oxidase (CCO). This leads to overactivation of glucose catabolism-related genes, excessive energy repertoire consumption, and subsequent hepatocyte pyroptosis. Single-cell RNA sequencing further confirmed the hyper-activation of glucose catabolism after metformin treatment. Altogether, we showed that functional Lepr is necessary for metformin treatment to be effective, and that long-term metformin treatment might promote NAFLD progression in leptin-insensitive individuals. This provides important insight into the clinical application of metformin.

This paper proposes a collaborative optimization strategy for speed planning and energy management of intelligent plug-in hybrid electric vehicles (PHEVs). In this study, a single-axis parallel PHEV with the powertrain of P2 configuration is employed as the research object. Then, dynamic programming (DP) is leveraged to ensure optimal fuel economy with the consideration of the simultaneous optimal demand torque distribution and autonomous speed selection. An adjustment coefficient that reasonably constrains the feasible domain of vehicle speed is designed to limit the range of autonomous speed selection according to driving conditions. The reasonableness of speed selection is enhanced by adding penalty functions to inhibit gear shifting and speed fluctuations. To consider the variability of the control strategies based on the constraints of travel time and distance, a time-domain and a space-domain collaborative optimization model are established respectively, and a simulation analysis of the collaborative optimization energy management strategy is conducted. The simulation result shows that the strategy achieves the collaborative optimization of speed autonomous planning and reasonable allocation for demand torque. In addition, the proposed strategy demonstrates preferable energy economy under different constraints based on time and space domains.

Sea surface height anomaly (SSHA) induced by tropical cyclones (TCs) is closely associated with oscillations and is a crucial proxy for thermocline structure and ocean heat content in the upper ocean. The prediction of TC-induced SSHA, however, has been rarely investigated. This study presents a new composite analysis-based random forest (RF) approach to predict daily TC wind pump induced SSHA. The proposed method utilizes TC's characteristics and prestorm upper oceanic parameters as input features to predict TC-induced SSHA up to 30 days after TC passage. Simulation results suggest that the proposed method is skillful at inferring both the amplitude and temporal evolution of SSHA induced by TCs of different intensity groups. Using a TC-centered 5° × 5° box, the proposed method achieves highly accurate prediction of TC-induced SSHA over the Western North Pacific with root mean square error of 0.024 m, outperforming alternative machine learning methods and the numerical model. Moreover, the proposed method also demonstrated good prediction performance in different geographical regions, i.e., the South China Sea and the Western North Pacific subtropical ocean. The study provides insight into the application of machine learning in improving the prediction of SSHA influenced by extreme weather conditions. Accurate prediction of TC-induced SSHA allows for better preparedness and response, reducing the impact of extreme events (e.g., storm surge) on people and property.

We aimed to identify potential molecular biomarkers through integrated analysis of microbiome and transcriptome data in colon cancer. Microbiome, transcriptome, and clinical phenotype data were downloaded from TCMA and TCGA databases. Intestinal flora subtypes were identified, followed by screening feature genes of each subtype. Univariate and LASSO Cox regression analyses were conducted to identify optimal prognostic genes to establish prognostic model. Survival, clinical phenotypes, pathways, and immune infiltration within different risk groups were compared. Three intestinal flora subtypes were identified: Proteobacteria, Fusobacteria, and Bacteroidetes subtypes. Bacteroidetes subtype tended to have worse survival. Feature genes of Bacteroidetes subtype were mainly implicated in immune-related functional terms, whereas those of Fusobacteria and Proteobacteria subtypes were mainly implicated in functions associated with inflammatory response and transcription, respectively. LASSO Cox regression identified 6 optimal prognostic genes: CSF1R, HLA-DOA, NOS3, HOXB4, PLA1A, and RPL3, to establish prognostic risk model. High-risk patients were associated with worse survival and had high proportions of Bacteroidetes subtype and high immune infiltration. Proteobacteria, Fusobacteria, and Bacteroidetes largely dominated the gut microbial flora in colon cancer patients. Prognostic model based on feature genes of intestinal flora subtypes can predict survival in colon cancer.

Oncogenic signaling pathways-guided alternative splicing events and their clinical prognostic values were investigated in lung squamous cell carcinoma (LUSC). RNAseq and AS data of LUSC were obtained from TCGA and SpliceSeq database, respectively. Pathway enrichment-guided activity study of alternative splicing (PEGASAS) analysis was performed to evaluate the activity of oncogenic pathways. We identified 4229 AS events in 2311 genes significantly associated with the Hallmark_Myc_Targets_V1 pathway. Twenty-nine prognostic Myc guided-AS events classified LUSC into 3 subtypes, of which Cluster 1 subtype showed the worst prognosis, while cluster 2 subtype showed a favorable prognosis. A prognostic model based on 10 most contributive prognostic AS events identified by LASSO could effectively stratify LUSC patients into high- and low-risk groups. The high-risk group was associated with worse survival and contained more samples in poor prognostic subtype (cluster 1). GSEA revealed that cell adhesion and immune response pathways were significantly enriched in the high-risk group, and AS pathways in the low-risk group. Fifty-nine regulatory SFs were identified to regulate these 10 AS events. Myc-guided AS events could classify LUSC samples into subtypes with significantly different survival. A prognostic model based on 10 Myc-guided AS events could predict the survival of LUSC.

Blue sprat (Spratelloides gracilis) is an economically valuable species that inhabits the central Taiwan Strait. However, despite the implementation of a local management scheme involving a closed season between 1 May and 1 June, the annual catch has rapidly decreased over the decades. Thus, the efficacy of the implemented regulations must be investigated. This study sought to clarify the reproductive biology, spawning ground, and behavior of this species in the waters of Penghu. In total, 6,549 specimens were collected between March 2021 and September 2022. Considering gonadosomatic index, group maturity, and oocyte diameter, we found that the spawning season (March–September) peaked in April; new cohorts were distinctly recruited after the spawning peak. The distribution of the spawning ground (latitude, 23°41′N to 23°43′N; longitude, 119°32′E to 119°39′E) was determined by considering the fishing area of mature females and DNA analysis of adhered eggs. We further noted shoals of fish darting in the bottom water without clear schooling movement, females’ abdomen frequently contacting substrata for eggs able to attach on during oviposition, and males releasing sperms making water milky white; these indicate that S. gracilis exhibits promiscuous spawning behavior. Our findings may facilitate the management and conservation of S. gracilis in this region.

In this study, an innovative transdermal peptide, #PKU12, was developed based on transdermal peptide TD-1, and the anti-tumor effect of PKU12-based siRNA against HPV was investigated in vivo. Furthermore, transcriptome differences between PKU12 + siRNA treatment and control groups were compared to assess treatment effects. The top five upregulated and downregulated genes identified by RNA sequencing were further subjected to survival analysis. The present study, for the first time, showed that this novel peptide could enhance the transdermal delivery of the siRNA targeting HPV16 L1, E6, and E7. PKU12-based siRNA delivery significantly repressed the mRNA expression levels of HPV16 L1, E6, and E7 in the SiHa xenograft tumors and attenuated tumor growth as well. The RNA-sequencing results showed that a total of 586 DEGs were detected in the PKU12 + siRNA-treated tumor tissues compared to the control tumor tissues. The GSEA analysis revealed that DEGs were inversely associated with the HIF-1 signaling pathway, the TNF signaling pathway, the AGE-RAGE signaling pathway, the NF-kappa B signaling pathway, ferroptosis, the IL-17 signaling pathway, ovarian steroidogenesis, and rheumatoid arthritis. Further functional enrichment analysis revealed that DEGs were significantly enriched in several key pathways, including cytokine–cytokine receptor interaction, the TNF signaling pathway, and the IL-17 signaling pathway. High expression of MYH1, MYH4, FGG, DEPP1, and ZBTB16 was associated with shorter overall survival of patients with cervical cancer; high expression of SULT1E1, RAB3C, CXCR3, and PROX2 was associated with longer overall survival of patients with cervical cancer. In conclusion, the transdermal peptide PKU12 is potentially a good candidate for a siRNA delivery vehicle for the treatment of cervical cancer.

Abstract Background Salivary glands produce saliva that play essential roles in digestion and oral health. Derivation of salivary gland organoids from pluripotent stem cells (PSCs) provides a powerful platform to model the organogenesis processes during development. A few studies attempted to differentiate PSCs into salivary gland organoids. However, none of them could recapitulate the morphogenesis of the embryonic salivary glands, and most of the protocols involved complicated manufacturing processes. Methods To generate PSC-derived salivary gland placodes, the mouse embryonic stem cells were first differentiated into oral ectoderm by treatment with BMP4 on day 3. Retinoic acid and bFGF were then applied to the cultures from day 4 to day 6, followed by a 4-day treatment of FGF10. The PSC-derived salivary gland placodes on day 10 were transplanted to kidney capsules to determine the regenerative potential. Quantitative reverse transcriptase–polymerase chain reaction, immunofluorescence, and RNA-sequencing were performed to identify the PSC-derived SG placodes. Results We showed that step-wise treatment of retinoic acid and FGF10 promoted the differentiation of PSCs into salivary gland placodes, which can recapitulate the early morphogenetic events of their fetal counterparts, including the thickening, invagination, and then formed initial buds. The PSC-derived salivary gland placodes also differentiated into developing duct structures and could develop to striated and excretory ducts when transplanted in vivo. Conclusions The present study provided an easy and safe method to generate salivary gland placodes from PSCs, which offered possibilities for studying salivary gland development in vitro and developing new cell therapies.

We analyze, for the first time in the oceanographic literature, pH over the top ~10 m of the sediment (down to 11.9 m) in a deep-sea environment, together with the oxidation/reduction potential and concentrations of solid organic carbon (OC) and CaCO3. A total of 1157 sediment cores were collected from years 2000 to 2011 over >300,000 km2 in the South China Sea, at water depths up to 3702 m. We found that there were marked downward pH increases in the upper 2 m of the sediment (first 20-40 ka, corresponding to the geochemically active period). In deeper, older sediment (up to 200 ka), pH was generally less variable with depth but not uniform, and solid OC may have been consumed down to ≥10 m depth. This reflected interactions between in situ geochemical diagenetic processes, which tended to create vertical variations, and vertical diffusion of ions, which tended to even out vertical variability. In other words, there were slow diagenetic geochemical processes in the sediment layer below 2 m, and the effects of these in situ processes were partly offset by vertical diffusion. Overall, our study identified a previously unknown consistent pH difference between the upper 2 m of the sediment and the underlying layer down to ≥10 m, and suggested combinations of geochemical diagenetic processes and vertical diffusion of ions in the porewater to explain it. These results provide a framework for further studies of pH in the top multi-meter layer of the sediment in the World Ocean.

Low glume coverage is the preferred for easy threshing in grain production, but the genetic basis remains unclear. Here, the authors report the gene GC1, which encodes an atypical G protein γ subunit, negatively regulates sorghum glume coverage and the naturally truncated alleles can be useful in the naked grain breeding.

Graph convolutional neural networks have received a lot of attention in various tasks dealing with graph data by aggregating information from neighboring nodes and passing node information. Many recent studies have looked at the impact of topological features on node classification tasks by altering aggregation based on degree values or incorporating topological data analysis into graph convolutional neural networks; however, graph data itself has many topological characteristics in complex networks. In most circumstances, the graph’s topological characteristics reveal the nodes’ similarity and facilitate the node classification task. This paper proposes a topological structure feature extraction method based on the concept of complex topological characteristics, which can obtain deeper topological features in the graph structure and use node features to obtain feature information that is more important for classification from both feature spaces. Evidence from experimental studies has established that the topological structure obtained by the method in this paper can be used as input to the GCN,and good results can be achieved on the classification task even without any external information on the nodes. In the graph dataset of connected topologies, the method exhibits a very large increase in accuracy and macro F1-score when compared to the state-of-the-art baseline model after mixing the node features.

BackgroundMidline shift (MLS) is troublesome problem that may occur in patients with a large infarct core (LIC) and may be related to the baseline infarct core volume. The purpose of this study was to explore the relationship between baseline infarct core volume and early MLS presence.Materials and methodsPatients with acute intracranial large artery occlusion and a pretreatment relative cerebral blood flow (rCBF) 40 ml based on an rCBF < 15% showed good predictive value for early MLS occurrence.

Male sterility is a common biological phenomenon in plant kingdom and has been used to generate male-sterile lines, which are important genetic resources for commercial hybrid seed production. Although increasing numbers of male-sterility genes have been identified in rice (Oryza sativa) and Arabidopsis (Arabidopsis thaliana), few male-sterility-related genes have been characterized in foxtail millet (Setaria italica). In this study, we isolated a male-sterile ethyl methanesulfonate-generated mutant in foxtail millet, no pollen 1 (sinp1), which displayed abnormal Ubisch bodies, defective pollen exine and complete male sterility. Using bulk segregation analysis, we cloned SiNP1 and confirmed its function with CRISPR/Cas9 genome editing. SiNP1 encoded a putative glucose-methanol-choline oxidoreductase. Subcellular localization showed that the SiNP1 protein was preferentially localized to the endoplasmic reticulum and was predominantly expressed in panicle. Transcriptome analysis revealed that many genes were differentially expressed in the sinp1 mutant, some of which encoded proteins putatively involved in carbohydrate metabolism, fatty acid biosynthesis, and lipid transport and metabolism, which were closely associated with pollen wall development. Metabolome analysis revealed the disturbance of flavonoids metabolism and fatty acid biosynthesis in the mutant. In conclusion, identification of SiNP1 provides a candidate male-sterility gene for heterosis utilization in foxtail millet and gives further insight into the mechanism of pollen reproduction in plants.

The Tashan coal mine is selected as a case study to determine the deformation and damage mechanisms of the lower roadway in a close-range residual coal pillar area. Roof drilling peephole technology is applied to detect the damage to the roadway roof surrounding rock. A boundary invisibility equation is derived for the plastic zone of a circular hole based on the theory of a butterfly plastic zone in a non-uniform stress field in which the principal stress occurs at an arbitrary angle to the vertical. Maple mathematical drawing software is combined with FLAC3D numerical simulations to investigate the influence of the principal stress ratio and direction on the roadway plastic zone. The results indicate that the plastic zone of the roadway surrounding rock assumes a butterfly shape when the bidirectional stress ratio is large, and the direction of the butterfly-shaped failure of the roadway is related to the principal stress direction. Field test images are combined to show that the asymmetric damage pattern of the lower roadway in a close-range residual coal pillar area is influenced by the presence of the roadway in a non-uniform stress field in which the main stress direction is deflected.

Abstract Background MR fingerprinting (MRF) is a novel imaging method proposed for the diagnosis of Multiple Sclerosis (MS). This study aims to determine if MR Fingerprinting (MRF) relaxometry can differentiate frontal normal appearing white matter (F-NAWM) and splenium in patients diagnosed with MS as compared to controls and to characterize the relaxometry of demyelinating plaques relative to the time of diagnosis. Methods Three-dimensional (3D) MRF data were acquired on a 3.0T MRI system resulting in isotropic voxels (1 × 1 × 1 mm3) and a total acquisition time of 4 min 38 s. Data were collected on 18 subjects paired with 18 controls. Regions of interest were drawn over MRF-derived T1 relaxometry maps encompassing selected MS lesions, F-NAWM and splenium. T1 and T2 relaxometry features from those segmented areas were used to classify MS lesions from F-NAWM and splenium with T-distributed stochastic neighbor embedding algorithms. Partial least squares discriminant analysis was performed to discriminate NAWM and Splenium in MS compared with controls. Results Mean out-of-fold machine learning prediction accuracy for discriminant results between MS patients and controls for F-NAWM was 65 % (p = 0.21) and approached 90 % (p

Abstract Patients with stroke are likely to experience impaired health-related quality of life (QOL), especially during the COVID-19 pandemic. This study aimed to evaluate the QOL of Chinese patients with stroke during the pandemic and explore the associated variables. A matched-pair, multicenter survey was conducted before and during the COVID-19 pandemic. Questionnaires including the 36-item Short-Form Health Survey (SF-36), the Activities of Daily Living (ADL) scale, and the Questionnaire about the Process of Recovery (QPR) were used. A total of 172 matched pairs (344 patients) were recruited in this study. Hierarchical multiple regression analysis was performed to analyze variables associated with QOL. Physical and mental component scores (PCS and MCS) were higher among the stroke patients during the pandemic (44.20 ± 18.92 and 54.24 ± 19.08) than before the pandemic (37.98 ± 14.52 and 43.50 ± 20.94). Pandemic stress, demographic and clinical characteristics were negative variables associated with PCS and MCS. QPR was positively associated with PCS and MCS. The QOL of Chinese stroke patients was higher during than before the COVID-19 pandemic. Pandemic stress aggravated stroke patients’ QOL, while personal recovery could alleviate the detrimental effect of pandemic stress on QOL for stroke patients.

A simple and efficient hydroxide-mediated SNAr rearrangement was reported to synthesize new depside derivatives containing the diaryl ether skeleton from the natural product barbatic acid. The prepared compounds were determined using 1H NMR, 13C NMR, HRMS, and X-ray crystallographic analysis and were also screened in vitro for cytotoxicity against three cancer cell lines and one normal cell line. The evaluation results showed that compound 3b possessed the best antiproliferative activity against liver cancer HepG2 cell line and low toxicity, which made it worth further study.

Barbatic acid, a compound isolated from lichen, has demonstrated a variety of biological activities. In this study, a series of esters based on barbatic acid (6a–q′) were designed, synthesized, and evaluated for their diuretic and litholytic activity at a concentration of 100 μmol/L in vitro. All target compounds were characterized using 1H NMR, 13C NMR, and HRMS, and the spatial structure of compound 6w was confirmed using X-ray crystallography. The biological results showed that some derivatives, including 6c, 6b′, and 6f′, exhibited potent diuretic activity, and 6j and 6m displayed promising litholytic activity. Molecular docking studies further suggested that 6b′ had an optimal binding affinity to WNK1 kinases related to diuresis, while 6j could bind to the bicarbonate transporter CaSR through a variety of forces. These findings indicate that some barbatic acid derivatives could be further developed into novel diuretic agents.

With the goal of automatic sea ice mapping during the summer sea ice melt cycle, this study involved designing a fully automatic sea ice segmentation method based on a deep learning semantic segmentation network applicable to summer SAR images, which achieved high accuracy and the fully automatic extraction of sea ice segmentation during the summer ice melt cycle by optimizing the process, improving the pixel-level semantic segmentation network, and introducing high-resolution sea ice concentration features. Firstly, a convolution-based, high-resolution sea ice concentration calculation method is proposed and was applied to the deep learning task. Secondly, the proposed DF-UHRNet network was improved upon by designing high- and low-level fusion modules, introducing an attention mechanism, and reducing the number of convolution layers and other operations, and it can effectively fuse high- and low-scale semantic features and global contextual information based on reducing the overall number of network parameters, enabling it to achieve pixel-level classification. The results show that this method meets the needs associated with the automatic mapping and high-precision classification of thin ice, one-year ice, open water, and multi-year ice and effectively reduces the model size.

In this paper, 30-slot/24-pole five-phase PMSM with hybrid single/double layer (HL) fractional-slot concentrated winding (FSCW) is designed for wheel-driving application in electric vehicles (EVs). Third harmonic current injection in different operating stages of the machine is investigated, including normal operation and fault-tolerant operation. HL FSCW machine is validated to be suitable for injecting third harmonic current to enhance torque by both theoretical analysis and finite-element analysis (FEA), and compared with 20-slot/24-pole single-layer (SL) and double-layer (DL) FSCW machine under constant rms and peak harmonic injection. Besides, a novel flux weakening control method with third harmonic current injection is proposed, which improves torque and efficiency of HL FSCW machine. The influence of nonlinearity caused by stator core saturation and higher order harmonics contained in back electromotive force (EMF) is included in flux weakening operation with harmonic injection. Finally, fault-tolerant control of HL FSCW machine with one-phase open-circuit fault is investigated, and two compensatory strategies with and without third harmonic current injection are proposed. Torque ripple caused by one-phase open-circuit fault is suppressed effectively by the proposed strategies.

Efficient and accurate monitoring of green tide is of great significance to marine disaster prevention and marine environment protection. A method is proposed in this article for the automatic extraction of the green tide from Chinese Gaofen-3 (GF-3) satellite synthetic aperture radar (SAR) images, which is based on feature selection and deep learning. In this article, since SAR images contain rich polarization information, we first employ H/A/α decomposition and other methods for the extraction of high-dimensional features from GF-3 SAR images. Second, a novel feature selection method for SAR images is designed by using the Bhattacharyya distance and the Separability index, which can select the optimal features subset with a strong ability for recognizing green tide and without correlation between features from the high-dimensional features of SAR. Then, to alleviate the model training burden and improve the prediction efficiency, a lightweight semantic segmentation network, called Mobile-SegNet, is designed based on MobileNets and SegNet. Finally, the selected optimal features and their labels are sent to Mobile-SegNet for training and obtaining the automatic recognition model of green tide, and in turn, the automatic extraction of green tide is achieved through model prediction. To verify the effectiveness of the proposed green tide extraction method, GF-3 SAR remote sensing images taken in 2020 that covered the Yellow Sea are collected and used in the green tide extraction experiment. The results show that the proposed method is available for an effective reduction of the feature dimension required for green tide extraction, and the improvement of the accuracy and efficiency of green tide detection. The overall accuracy, F1-score, mean intersection over union, and the kappa coefficient of the proposed method reached 99.52%, 95.76%, 92.19%, and 0.92, respectively.

Background The effectiveness of a nurse‐led in‐hospital monitoring protocol with mobile ECG (iECG) was investigated for detecting atrial fibrillation in patients post‐ischemic stroke or post‐transient ischemic attack. The study aimed to assess the cost‐effectiveness of using iECG during the initial hospital stay compared with standard 24‐hour Holter monitoring. Methods and Results A Markov microsimulation model was constructed to simulate the lifetime health outcomes and costs. The rate of atrial fibrillation detection in iECG and Holter monitoring during the in‐hospital phase and characteristics of modeled population (ie, age, sex, CHA2DS2‐VASc) were informed by patient‐level data. Costs related to recurrent stroke, stroke management, medications (new oral anticoagulants), and rehabilitation were included. The cost‐effectiveness analysis outcome was calculated as an incremental cost per quality‐adjusted life‐year gained. As results, monitoring patients with iECG post‐stroke during the index hospitalization was associated with marginally higher costs (A$31 196) and greater benefits (6.70 quality‐adjusted life‐years) compared with 24‐hour Holter surveillance (A$31 095 and 6.66 quality‐adjusted life‐years) over a 20‐year time horizon, with an incremental cost‐effectiveness ratio of $3013/ quality‐adjusted life‐years. Monitoring patients with iECG also contributed to lower recurrence of stroke and stroke‐related deaths (140 recurrent strokes and 20 deaths avoided per 10 000 patients). The probabilistic sensitivity analyses suggested iECG is highly likely to be a cost‐effective intervention (100% probability). Conclusions A nurse‐led iECG monitoring protocol during the acute hospital stay was found to improve the rate of atrial fibrillation detection and contributed to slightly increased costs and improved health outcomes. Using iECG to monitor patients post‐stroke during initial hospitalization is recommended to complement routine care.

The mechanisms underlining pathogenesis of polycystic ovary syndrome (PCOS) remain largely unknown. Dysfunction of ovarian granulosa cells plays an important role. The present study performed the lncRNA and mRNA profiling by whole genome transcriptomic sequencing of ovary granulosa cells from women with PCOS and investigated the potential role of differentially expressed gens (DEGs) in the pathomechanism of PCOS. In total, 1,936 DEGs (30 upregulated and 1,906 downregulated mRNAs and lncRNAs) were identified in the ovary granulosa cells between control and PCOS group. Functional enrichment analysis showed that DEGs were mainly associated with cytokine–cytokine receptor interaction, neuroactive ligand–receptor interaction, and olfactory transduction. qRT-PCR validated the upregulation of DLGAP5 mRNA in ovary from PCOS group when compared to control group. Immunostaining and TUNEL assays showed that DLGAP5 protein level was increased while apoptosis was decreased in follicles of ovary in PCOS group. In vitro functional assays showed that DLGPA5 knockdown repressed viability and proliferation, but enhanced apoptosis and disrupted cell cycle in granulosa cells; while DLGAP5 overexpression had the opposite effects in granulosa cells. In conclusion, the study showed differentially expressed lncRNA and mRNA profile in the granulosa cells in ovaries of PCOS. Functional results demonstrated that DLGAP5 is a dysregulated candidate gene in the pathogenesis of PCOS, especially granulosa cell apoptosis and proliferation.

Human brain bank is the foundation for neurology and neuroscience, which provides research materials for medical scientists to explore what happen in human brains. Through voluntary postmortem brain tissue donation, brain bank collects, classifies, stores and distributes brain tissue samples for researchers with appropriate research proposals, so as to facilitate researchers to conduct human brain research. History showed that the act of brain only autopsy distinguished neurology as a distinct discipline. The emerges of brain banking accompanied with the advances of neurology and neuroscience. It facilitates the development of neurology from neuropathological examination feedback about the clinical presentations of the brain donor, plays an important role in the definition of novel neurological diseases, and also makes an extraordinary contribution to the disease mechanisms and novel therapeutic discoveries. This manuscript elaborated the history, current situation, and the impacts of human brain banking on current neurology. Furthermore, we discussed about the opportunities and challenges of brain banking in China. DOI:10.3969/j.issn.1672⁃6731.2020.10.012

Abstract Background The global epidemic of diabetes mellitus continues to grow and affects developed and developing countries alike. Intensive glycemic control is thought to modify the risks for vascular complications, hence the risks for diabetes-related death. We investigated the trend of diabetic vascular complication-related deaths between 2000 and 2016 in the global diabetes landscape. Methods We collected 17 years of death certificates data from 108 countries in the World Health Organization mortality database between 2000 and 2016, with coding for diabetic complications. Crude and age-standardized proportions and rates were calculated. Trend analysis was done with annual average percentage change (AAPC) of rates computed by joinpoint regression. Results From 2000 through 2016, 7,108,145 deaths of diabetes were reported in the 108 countries. Among them, 26.8% (1,904,787 cases) were attributed to vascular complications in damaged organs, including the kidneys (1,355,085 cases, 71.1%), peripheral circulatory (515,293 cases, 27.1%), nerves (28,697 cases, 1.5%) and eyes (5751 cases, 0.3%). Overall, the age-standardized proportion of vascular complication-related mortality was 267.8 [95% confidence interval (95% CI), 267.5–268.1] cases per 1000 deaths and the rate was 53.6 (95% CI 53.5–53.7) cases per 100,000 person-years. Throughout the 17-year period, the overall age-standardized proportions of deaths attributable to vascular complications had increased 37.9%, while the overall age-standardized mortality rates related to vascular complications had increased 30.8% (AAPC = 1.9% [1.4–2.4%, p

Background and Purpose Paroxysmal atrial fibrillation (PAF) underlying acute stroke frequently evades detection by standard practice, considered to be a combination of routine electrocardiogram (ECG) monitoring, and 24-hour Holter recordings. We hypothesized that nurse-led in-hospital intermittent monitoring approach would increase PAF detection rate. Methods We recruited patients hospitalised for stroke/transient ischemic attack, without history of atrial fibrillation (AF), in a prospective multi-centre observational study. Patients were monitored using a smartphone-enabled handheld ECG (iECG) during routine nursing observations, and underwent 24-hour Holter monitoring according to local practice. The primary outcome was comparison of AF detection by nurse-led iECG versus Holter monitoring in patients who received both tests: secondary outcome was oral anticoagulant commencement at 3-month following PAF detection. Results One thousand and seventy-nine patients underwent iECG monitoring: 294 had iECG and Holter monitoring. AF was detected in 25/294 (8.5%) by iECG, and 8/294 (2.8%) by 24-hour Holter recordings (P

Maternal betaine was reported to regulate offspring hepatic cholesterol metabolism in mammals. However, it is unclear whether and how feeding betaine to laying hens affects hepatic cholesterol metabolism in offspring chickens. Rugao yellow-feathered laying hens (n = 120) were fed basal or 0.5% betaine-supplemented diet for 28 D before the eggs were collected for incubation. Maternal betaine significantly decreased the hepatic cholesterol content (P

Abstract Background Organ replacement regenerative therapy based on human adult stem cells may be effective for salivary gland hypofunction. However, the generated tissues are immature because the signaling factors that induce the differentiation of human salivary gland stem cells into salivary glands are unknown. Methods Isolated human submandibular gland stem/progenitor cells (hSMGepiS/PCs) were characterized and three-dimensionally (3D) cultured to generate organoids and further induced by fibroblast growth factor 10 (FGF10) in vitro. The induced spheres alone or in combination with embryonic day 12.5 (E12.5) mouse salivary gland mesenchyme were transplanted into the renal capsules of nude mice to assess their development in vivo. Immunofluorescence, quantitative reverse transcriptase-polymerase chain reaction, calcium release analysis, western blotting, hematoxylin–eosin staining, Alcian blue–periodic acid-Schiff staining, and Masson’s trichrome staining were performed to assess the structure and function of generated tissues in vitro and in vivo. Results The isolated hSMGepiS/PCs could be long-term cultured with a stable genome. The organoids treated with FGF10 [FGF10 (+) group] exhibited higher expression of salivary gland–specific markers; showed spatial arrangement of AQP5+, K19+, and SMA+ cells; and were more sensitive to the stimulation by neurotransmitters than untreated organoids [FGF10 (−) group]. After heterotopic transplantation, the induced cell spheres combined with mouse embryonic salivary gland mesenchyme showed characteristics of mature salivary glands, including a natural morphology and saliva secretion. Conclusion FGF10 promoted the development of the hSMGepiS/PC-derived salivary gland organoids by the expression of differentiation markers, structure formation, and response to neurotransmitters in vitro. Moreover, the hSMGepiS/PCs responded to the niche in mouse embryonic mesenchyme and further differentiated into salivary gland tissues with mature characteristics. Our study provides a foundation for the regenerative therapy of salivary gland diseases.

Abstract Background Cases of Wallerian degeneration of bilateral cerebral peduncles after acute carbon monoxide poisoning have not yet been reported. To date, most of the delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) lesions captured in magnetic resonance imaging (MRI) has been located in the subcortical white matter and basal ganglia. Here we report two cases of DEACMP with abnormalities in the bilateral cerebral peduncles. The etiology of abnormalities, which were strictly confined to the bilateral cerebral peduncles, was Wallerian degeneration secondary to upstream nerve axonal damage, making this the first report on such bilateral cerebral peduncle abnormalities after DEACMP. Case presentation In this report, we present two cases of DEACMP with abnormal signals in the bilateral cerebral peduncles captured during brain MRIs. Case 1 was of a 68-year-old man who presented with paroxysmal disturbance of the consciousness, left limb weakness for 16 days, and lagging responses for 2 days. Case 2 was of a 55-year-old man who was unconscious for 6 h. In addition to the above mentioned characteristics on the brain MRIs, the electroencephalography of case 1 indicated that his forehead scans had a mixture of wide sharp, sharp, and three-phase waves. Brain diffusion tensor imaging of case 2 further proved that the bilateral cerebral anomalies represented Wallerian degeneration secondary to upstream axonal damage. After the definitive diagnosis, the patients returned to the local hospital for hyperbaric oxygen therapy. Conclusions Wallerian degeneration of the bilateral cerebral peduncles after acute carbon monoxide poisoning has never been reported before. The abnormal signals in the bilateral cerebral peduncles captured during brain MRIs indicated Wallerian degeneration secondary to upstream axonal damage; thus, these two cases may further our understanding of DEACMP imaging.

Abstract Background Parthenogenetic stem cells (PSCs) are a promising source of regenerated cardiomyocytes; however, their application may be limited without a paternal genome. Insulin-like growth factor-II (IGF-II), a paternally expressed growth hormone, is critical in embryonic differentiation. This study investigated whether forced expression of IGF-II in PSCs can accelerate their differentiation. Methods Overexpression and re-knockdown of IGF-II in PSCs were performed to investigate the role of IGF-II in PSC differentiation. The derivatives of PSCs with different IGF-II manipulations were transplanted into infarcted murine hearts to investigate the role of IGF-II in cardiomyocyte differentiation in vivo. Results Data showed that the expression of cardiac troponin T and troponin I in IGF-II-PSC outgrowths preceded that of parental PSC outgrowths, suggesting that IGF-II can accelerate PSC differentiation into cardiac lineage. Overexpression of IGF-II accelerated PSC differentiation towards cardiomyocytes while inhibiting PSC proliferation via the IGF-II/IGF1R signaling. Similar to that observed in cardiac marker expression, on differentiation day 24, IGF-II-PSCs showed PCNA and cyclin D2 expression comparable to juvenile mouse cardiomyocytes, showing that IGF-II-PSCs at this stage possess differential and proliferative properties similar to those of juvenile cardiomyocytes. Moreover, the expression pattern of cardiac markers in IGF-II-overexpressing PSC derivatives resembled that of juvenile mouse cardiomyocytes. After transplantation into the infarcted mouse hearts, IGF-II-PSC-derived cardiomyocytes displayed significant characteristics of mature cardiomyocytes, and IGF-II-depletion by shRNA significantly reversed these effects, suggesting the critical role of IGF-II in promoting cardiomyocyte maturation in vivo. Furthermore, IGF-II-overexpressing PSC derivatives reduced collagen deposition and mitochondrial damage in the infarcted areas and improved cardiac function. The re-knockdown of IGF-II could counteract these favorable effects of IGF-II. Conclusions These findings suggest that the ectopic expression of IGF-II accelerates PSC differentiation into the cardiac lineage and promotes cardiomyocyte maturation. The underlying process includes the IGF-II/IGF1R signaling, which is involved in the suppressive effect of IGF-II on PSC proliferation. Moreover, transplanting IGF-II-overexpressing PSC derivatives into the infarcted heart could reduce collagen deposition and improve mitochondria biogenesis and measurements of cardiac function, highlighting the importance of IGF-II in the application of PSCs in cardiac regeneration.

Background: Cancer is considered one of the most lethal diseases worldwide. Venous thromboembolism (VTE) is the second leading cause of death in cancer patients. As one of the most reproducible predictors of thromboembolism, the D-dimer level is commonly considered by oncologists. Previous studies have demonstrated that the most correlated genes at the D-dimer level are F3, F5 and FGA.Methods: Using data from TCGA and multiple webtools, including GEPIA2, UALCAN, TIMER2.0, Kaplan-Meier Plotter and CIBERSORTx, we analyzed the tumor mutation burden (TMB), microsatellite instability (MSI) and functions of D-dimer-related genes in cancer. Validation was conducted via quantitative real-time polymerase chain reaction (qRT-PCR) and independent GEO + GTEx cohort. All statistical analyses were performed in R software and GraphPad Prism 9.Results: F3, F5 and FGA were expressed differently in multiple cancer types. TMB, MSI and anti-PD1/PDL1 therapy responses were correlated with D-dimer-related gene expression. D-Dimer-related genes expression affect the survival of cancer patients. F3 and F5 functioned in TGF-beta signaling. F3 and F5 were related to immunity and affected the fraction of CD8+ T cells by upregulating the TGF-beta signaling pathway, forming an F3, F5/TGF-beta signaling/CD8+ T cell axis.Conclusion: F3, F5 and FGA serve as satisfactory GC multibiomarkers and potentially influence the immune microenvironment and survival of cancer patients by influencing TGF-beta signaling.

As maritime transportation develops, the pressure of port traffic increases. To improve the management of ports and the efficiency of their operations, vessel scheduling must be optimized. The vessel scheduling problem can be divided into channel scheduling and berth allocation. We considered the complex problem of vessel scheduling in a restricted channel and the berth allocation problem, and a combined model that considers carbon emissions was developed. This model should reduce vessel waiting times, improve the quality of the berth loading and unloading service, meet the requirements of “green” shipping, and improve the overall scheduling efficiency and safety of ports. An adaptive, double-population, multi-objective genetic algorithm NSGA-II-DP is proposed to calculate the mathematical model. In the case study, the rationality verification and sensitivity analysis of the model and algorithm are conducted, and the NSGA-II-DP and NSGA-II were compared. Results demonstrate that the overall convergence of the NSGA-II-DP algorithm is better than that of NSGA-II, demonstrating that the NSGA-II-DP algorithm is a useful development of NSGA-II. In terms of port scheduling, the results of our model and algorithm, compared with the decisions provided by the traditional First Come First Service (FCFS) strategy, are more in line with the requirements for efficiency and cost in the actual port management, and more dominant in the port management can provide better decision support for the decision-makers.

The recent ongoing outbreak of novel coronavirus SARS-CoV-2 (known as COVID-19) is a severe threat to human health worldwide. By press time, more than 3.3 million people have died from COVID-19, with many countries experiencing peaks in infections and hospitalizations. The main symptoms of infection with SARS-CoV-2 include fever, chills, coughing, shortness of breath or difficulty breathing, fatigue, muscle or body aches and pains. While the symptoms of the pandemic (H1N1) 2009 virus have many similarities to the signs and transmission routes of the novel coronavirus, e.g., fever, cough, sore throat, body aches, headache, chills and fatigue. And a few cases of serious illness, rapid progress, can appear viral pneumonia, combined with respiratory failure, multiple organ function damage, serious people can die. Therefore, there is an urgent need to develop a rapid and accurate field diagnostic method to effectively identify the two viruses and treat these early infections on time, thus helping to control the spread of the disease. Among molecular detection methods, RT-LAMP (real-time reverse transcription-loop-mediated isothermal amplification) has some advantages in pathogen detection due to its rapid, accurate and effective detection characteristics. Here, we combined the primers of the two viruses with the fluorescent probes on the RT-LAMP detection platform to detect the two viruses simultaneously. Firstly, RT-LAMP method was used respectively to detect the two viruses at different concentrations to determine the effectiveness and sensitivity of probe primers to the RNA samples. And then, the two virus samples were detected simultaneously in the same reaction tube to validate if testing for the two viruses together had an impact on the results compared to detecting alone.We verified the detection efficiency of three highly active BST variants during RT-LAMP assay. We expect that this assay can effectively and accurately distinguish COVID-19 from the pandemic (H1N1) 2009, so that these two diseases with similar symptoms can be appropriately differentiated and treated.

In this study, a novel hexagonal-YFeO3 (abbreviated as h-YFeO3) nanomaterial with stable room temperature ferromagnetic properties was synthesized by a two-step self-assembly approach. This nanomaterial with three-dimensional (abbreviated as 3D) frame architecture is homogeneously assembled by h-YFeO3 nanocrystalline with a diameter around 10–20 ​nm. As the annealing temperature rose from 823 ​K to 923 ​K, the structure of YFeO3 transformed from amorphous phase to P63/mmc hexagonal crystal type during the self-assembly process due to the combustion of urea, while P63cm type crystal generated at 873 ​K. The magnetic hysteresis loops recorded by vibrating sample magnetometry at 273–303 ​K, which displayed a transition from antiferromagnetic (paramagnetic) to ferromagnetic order. This ferromagnetic behavior related to the violation in inversion symmetry of hexagonal YFeO3 structure, causing by a greater distortion in nanocrystal boundary of perovskite-like structure and an increase in asymmetric covalent Y–O bonding. The ferromagnetic properties of h-YFeO3 3D nanomaterial were tested and found to be stable at room temperature (273 ​K–303 ​K), with maximum magnetization (Mm) value of h-YFeO3 3D nanomaterial reaching 2.6 ​A ​m2/g, 11 times higher than YFeO3 nanoparticle (20–50 ​nm). In sum, these findings look promising for future large-scale production of the advanced and inexpensive ferromagnetic perovskite-structure materials at room temperature as well as in magnetic application.

Abstract Background Treatment with metformin, the biguanide of hepatic insulin sensitizer, in patients with non-alcoholic fatty liver disease (NAFLD) has been reported with contradictory findings regarding the effectiveness on blood lipids and liver histology. In this study, we aimed to explore the preventive effects of metformin on NAFLD in Zucker diabetic fatty (ZDF) rats. Methods Male ZDF rats and Zucker lean rats aged 4–8 weeks were subjected to vehicle or metformin treatment for 6 months. Liver cDNA microarray assay, and protein semiquantitative and histological examinations were performed. Results Data demonstrated that ZDF rats developed hyperglycemia, hyperlipidemia, liver deficiency and hepatocyte degeneration. The metformin treatment significantly reduced post-load blood glucose levels, but not blood lipid profiles or liver enzyme levels. Hepatocyte degeneration was not attenuated after the treatment. The metformin-treated ZDF rats showed activation of AMP-activated protein kinase by Western blot and overexpression of cytochrome c oxidase by immunofluorescent microscopy. Gene expression microarray assay demonstrated that a panel of genes participating in glucose and lipid metabolisms were changed in the ZDF rats, and most of the altered genes involved in glucose and cholesterol metabolisms, but not those in fatty acid metabolisms, were corrected by the metformin treatment. No genes associated with inflammation, apoptosis, fibrosis, or cell death were overexpressed in the metformin-treated ZDF rats. Conclusions These results suggest that long-term metformin treatment presents no preventive effect for NAFLD in ZDF rats.